Biomedical ultrasound, at frequencies of approximately 1-2 MHz and intensities of approximately 1-30 W/sq.cm causes a number of non-thermal biological effects in both plant roots and cultured mammalian cells. These effects include decreased growth, cell cycle perturbations, perturbations in macromolecular syntheses, and induction of chromosomal anomalies in plant and roots; and lysis, loss of viability, decreased growth rate, and increased giant cell formation in cultured mammalian cells. The proposed research has two major objectives: (1) to expand our understanding of ultrasound effects on mammalian cells using an in vitro system, and (2) to determine if and to what extent ultrasound effects observed in plant roots and cultured cells also occur in mammalian cells in vivo. The in vitro studies will be carried out using Chinese hamster ovary (CHO) cells, and will include examination of ultrasound effects on the following endpoints related to cell regulatory and genetic function: cell cycle kinetics, ultrasound sensitivity as a function of cell cycle position, chromosomal anomalies, chromosome banding patterns, satellite DNA analyses, single and double strand DNA breaks, and DNA-protein crosslinks. The in vivo studies will utilize Chinese hamster cheek pouch epithelium and regenerating livers, and the endpoints examined will include: cell cycle kinetics, chromosomal anomalies, and chromosomal banding patterns. The results obtained should be directly relevant to assessments of the safety of diagnostic and therapeutic applications of ultrasound. The endpoints examined in the in vitro studies include several parameters (e.g. chromosomal anomalies, DNA strand analyses) which may be indicators of possible mutagenicity. The in vivo studies include some of the same endpoints and should also give an indication of the extent to which extrapolation to mammalian in vivo systems is possible from the existing body of knowledge concerning ultrasound effects in plants and on cultured mammalian cells.